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. 2023 Dec 14;95(1):37-43.
doi: 10.1136/jnnp-2023-331799.

Prognostic value of spinal cord lesion measures in early relapsing-remitting multiple sclerosis

Markus Lauerer  1   2 , Julian McGinnis  1   3 , Matthias Bussas  1   2 , Malek El Husseini  4 , Viola Pongratz  1   2 , Christina Engl  1 , Alexander Wuschek  1 , Achim Berthele  1 , Isabelle Riederer  4 , Jan S Kirschke  4 , Claus Zimmer  4 , Bernhard Hemmer  1   5 , Mark Mühlau  6   2
Affiliations

Prognostic value of spinal cord lesion measures in early relapsing-remitting multiple sclerosis

Markus Lauerer et al. J Neurol Neurosurg Psychiatry. .

Abstract

Background: Spinal cord (SC) lesions have been associated with unfavourable clinical outcomes in multiple sclerosis (MS). However, the relation of whole SC lesion number (SCLN) and volume (SCLV) to the future occurrence and type of confirmed disability accumulation (CDA) remains largely unexplored.

Methods: In this monocentric retrospective study, SC lesions were manually delineated. Inclusion criteria were: age between 18 and 60 years, relapsing-remitting MS, disease duration under 2 years and clinical follow-up of 5 years. The first CDA event after baseline, determined by a sustained increase in the Expanded Disability Status Scale over 6 months, was classified as either progression independent of relapse activity (PIRA) or relapse-associated worsening (RAW). SCLN and SCLV were compared between different (sub)groups to assess their prospective value.

Results: 204 patients were included, 148 of which had at least one SC lesion and 59 experienced CDA. Patients without any SC lesions experienced significantly less CDA (OR 5.8, 95% CI 2.1 to 19.8). SCLN and SCLV were closely correlated (rs=0.91, p<0.001) and were both significantly associated with CDA on follow-up (p<0.001). Subgroup analyses confirmed this association for patients with PIRA on CDA (34 events, p<0.001 for both SC lesion measures) but not for RAW (25 events, p=0.077 and p=0.22).

Conclusion: Patients without any SC lesions are notably less likely to experience CDA. Both the number and volume of SC lesions on MRI are associated with future accumulation of disability largely independent of relapses.

Keywords: MRI; clinical neurology; image analysis; multiple sclerosis.

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Conflict of interest statement

Competing interests: VP has received research funding from Novartis (Oppenheim Förderpreis 2017). AB has received consulting and/or speaker fees from Alexion, Biogen, Celgene, Horizon, Novartis, Roche and Sandoz/Hexal. His institution has received compensation for clinical trials from Alexion, Biogen, Merck, Novartis, Roche, and Sanofi Genzyme. JSK has received research funding from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG; project 432290010), the German Federal Ministry of Education and Research (13GW0469D) and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (101045128—iBack-epic—ERC-2021-COG). He is Co-Founder of Bonescreen. BH has served on scientific advisory boards for Novartis; he has served as DMSC member for AllergyCare, Sandoz, Polpharma, Biocon and TG therapeutics; his institution received research grants from Roche for multiple sclerosis research. He has received honoraria for counseling (Gerson Lehrmann Group). He holds part of two patents; one for the detection of antibodies against KIR4.1 in a subpopulation of patients with multiple sclerosis and one for genetic determinants of neutralising antibodies to interferon.

Figures

Figure 1
Figure 1
Patient flow chart. CDA, confirmed disability accumulation; EDSS, Expanded Disability Status Scale; RRMS, relapsing-remitting multiple sclerosis; SC, spinal cord.
Figure 2
Figure 2
Rate of CDA on follow-up in patients with and without SC lesions. Bar plot showing percentages of disability worsening in both groups. Fisher’s exact test was performed for between-group comparison. CDA, confirmed disability accumulation; SC, spinal cord.
Figure 3
Figure 3
SC lesion measures in patients with and without CDA on follow-up. (A) Dot plot showing the number of spinal lesions in both groups. The black dots represent the median for the respective group, while the black lines give the IQR. (B) Box/violin plot showing lesion volume in both groups. The y-axis has been log-scaled for better visualisation. P values in parentheses are calculated for the subgroup of patients with at least one spinal lesion. Wilcoxon-Mann Whitney tests were performed in all cases. (C) Receiver operating characteristic curves for both SC lesion measures with CDA as outcome parameter. Between-curve comparison was performed according to the method described by DeLong et al for paired data. AUC, area under the curve; CDA, confirmed disability accumulation; SC, spinal cord.
Figure 4
Figure 4
SC lesion measures in patients with either RAW or PIRA activity as a confirmed disability accumulation event on follow-up. (A) Dot plot showing the number of spinal lesions in both groups. The black dots represent the median for the respective group, while the black lines give the IQR. (B) Box/violin plot showing lesion volume in both groups. The y-axis has been log-scaled for better visualisation. Wilcoxon-Mann Whitney tests were performed in all cases. (C) Receiver operating characteristic curves for both SC lesion measures with PIRA versus RAW as outcome parameter. Between-curve comparison was performed according to the method described by DeLong et al for paired data. AUC, area under the curve; PIRA, progression independent of relapse activity; RAW, relapse-associated worsening; SC, spinal cord.
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